Asentra

CHARACTERISTICS OF THE MEDICINAL PRODUCT

1. NAME OF THE MEDICINAL PRODUCT

Asentra, 50 mg, film-coated tablets
Asentra, 100 mg, film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Asentra, 50 mg, film-coated tablets:
Each film-coated tablet contains 55.95 mg of sertraline hydrochloride, equivalent to 50 mg of sertraline
(Sertralinum).
Asentra, 100 mg, film-coated tablets:
Each film-coated tablet contains 111.90 mg of sertraline hydrochloride, equivalent to 100 mg of sertraline
(Sertralinum).
A full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet
White, round, film-coated tablets with a score line on one side.
The tablet can be divided into equal doses.

4. CLINICAL PARTICULARS

4.1 Therapeutic Indications

Sertraline is indicated for the treatment of:

• Major depressive episodes. Prevention of recurrence of major depressive episodes.
• Panic disorder with or without agoraphobia.
• Obsessive-compulsive disorder (OCD) in adults and children and adolescents aged 6-17 years.
• Social anxiety disorder.
• Post-traumatic stress disorder (PTSD).

4.2 Posology and Method of Administration

Dosage
Initiation of treatment
Depression and OCD
Sertraline treatment should be started at a dose of 50 mg per day.
Panic disorder, PTSD, and social anxiety disorder
Treatment should be started at a dose of 25 mg per day. After one week, the dose should be increased to 50 mg once daily. This dosing regimen reduces the frequency of common adverse events associated with the initial treatment of panic disorder.
Dose increases
Depression, OCD, panic disorder, social anxiety disorder, and PTSD
Patients who do not respond to a dose of 50 mg may benefit from dose increases. Dose changes should be made at intervals of at least one week, each time increasing the dose by 50 mg, up to a maximum dose of 200 mg per day. Given the long elimination half-life of sertraline (approximately 24 hours), dose changes should not be made more frequently than once a week.
The onset of therapeutic effect may occur within 7 days, but it usually requires more time (especially for OCD).
Maintenance treatment
During long-term maintenance treatment, the dosage should be kept at the lowest level that maintains a therapeutic effect, and then adjusted according to need.
Depression
Long-term treatment may also be necessary to prevent recurrence of major depressive episodes. In most cases, the recommended dose is the same as that used during the current episode. Patients with depression should be treated for at least 6 months to ensure that the symptoms of the disorder have disappeared.
Panic disorder and OCD
In the case of panic disorder and OCD, the need for continued treatment should be regularly assessed, as the ability to prevent relapse has not been demonstrated in these disorders.
Elderly patients
In elderly patients, the medicinal product should be used with caution, as they may have an increased risk of hyponatremia (see section 4.4).
Patients with liver dysfunction
In patients with liver dysfunction, sertraline should be used with caution. Smaller doses of the medicinal product or less frequent administration should be used (see section 4.4). Since there are no clinical data, sertraline should not be used in patients with severe liver dysfunction (see section 4.4).
Patients with renal impairment
In patients with renal impairment, dose adjustment is not required (see section 4.4).
Children and adolescents
Use in children and adolescents with OCD
Age 6-12 years: initially 25 mg once daily. After one week, the dose may be increased to 50 mg once daily.
Age 13-17 years: initially 50 mg once daily.
If there is no response to a dose of 50 mg per day, subsequent doses may be higher in subsequent weeks, depending on the needs. The maximum dose is 200 mg per day.
When increasing the daily dose above 50 mg, consideration should be given to the smaller body mass of children compared to adults. Dose changes should not be made more frequently than once a week.
The efficacy of the medicinal product has not been demonstrated in the treatment of major depressive episodes in children.
There are no available data on the use of the medicinal product in children under 6 years of age (see section 4.4).

• 4.4).

Method of administration
Sertraline should be administered once daily, in the morning or evening.
Tablets can be taken with or without food.
Withdrawal symptoms after discontinuation of sertraline:
Abrupt discontinuation of the medicinal product should be avoided. To reduce the risk of withdrawal symptoms, the dose of the medicinal product should be gradually decreased over at least one to two weeks before discontinuation of treatment with Asentra (see sections 4.4 and 4.8).
If disturbing symptoms occur during dose reduction or after treatment discontinuation, consideration should be given to resuming the previous dose. The doctor may also continue to reduce the dose, but more slowly and with greater caution.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Concomitant use of irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of serotonin syndrome, which is characterized by symptoms such as psychomotor agitation, tremor, and hyperthermia. Sertraline should not be initiated within at least 14 days after discontinuation of an irreversible MAOI. Sertraline should be discontinued for at least 7 days before starting treatment with an irreversible MAOI (see section 4.5).
Concomitant use of pimozide is contraindicated (see section 4.5).

4.4 Special Warnings and Precautions for Use

Serotonin syndrome (SS) or neuroleptic malignant syndrome (NMS)
The development of life-threatening syndromes, such as serotonin syndrome (SS) or neuroleptic malignant syndrome (NMS), has been observed in individuals using SSRIs, including sertraline. The risk of SS or NMS increases when serotonergic agents (including other serotonergic antidepressants, amphetamine derivatives, tryptans) are used concomitantly with medicinal products that disrupt serotonin metabolism (including MAOIs, e.g., methylene blue), antipsychotics, and other dopamine antagonists, and opioids (including buprenorphine). The patient should be monitored for signs and symptoms of SS or NMS (see section 4.3).
If concomitant use of other serotonergic agents is clinically justified, careful observation of the patient is recommended, especially during the initial phase of treatment and during dose increases.
Symptoms of serotonin syndrome may include changes in mental status, autonomic instability, neuromuscular abnormalities, or gastrointestinal symptoms.
If serotonin syndrome is suspected, consideration should be given to reducing the dose or discontinuing treatment, depending on the severity of the symptoms.
Switching from selective serotonin reuptake inhibitors (SSRIs), antidepressants, or anti-obsessional agents
There are limited data from controlled trials on the optimal timing of switching from an SSRI, antidepressant, or anti-obsessional agent to sertraline. When switching, caution and sound medical judgment should be exercised, especially when switching from long-acting agents, such as fluoxetine.
Other serotonergic agents, e.g., tryptophan, fenfluramine, and 5-HT agonists
Concomitant use of sertraline with other medicinal products that enhance serotonergic neurotransmission, such as amphetamine derivatives, tryptophan, or fenfluramine, or 5-HT agonists, or herbal products containing St. John's Wort (Hypericum perforatum), should be done with caution and, if possible, avoided, due to the potential for pharmacodynamic interactions.
QTc prolongation/torsade de pointes-type ventricular tachycardia
Reports of QTc prolongation and torsade de pointes-type ventricular tachycardia have been received during the post-marketing period for sertraline. Most of the reports were in patients with other risk factors for QTc prolongation/torsade de pointes.
A thorough QTc study in healthy volunteers has shown that sertraline has a mild effect on QTc interval prolongation. A positive correlation between sertraline exposure and QTc interval prolongation has been demonstrated. Therefore, sertraline should be used with caution in patients with additional risk factors for QTc prolongation/torsade de pointes, such as cardiac disease, hypokalemia, or hypomagnesemia, a positive family history of QTc prolongation, and concomitant use of medicinal products that prolong the QTc interval (see sections 4.5 and 5.1).
Activation of hypomania or mania
In a small number of patients treated with marketed antidepressants and anti-obsessional agents, including sertraline, symptoms of hypomania or mania have been observed.
Therefore, sertraline should be used with caution in patients with a history of mania or hypomania. Close monitoring by the physician is required. Sertraline should be discontinued in any patient entering a manic phase.
Schizophrenia
In patients with schizophrenia, there may be an exacerbation of psychotic symptoms.
Seizures
Seizures have been reported in patients treated with sertraline. Sertraline should be avoided in patients with unstable epilepsy, and patients with controlled epilepsy should be carefully monitored. Sertraline should be discontinued in any patient who develops seizures.
Suicide, suicidal thoughts, suicide attempts, or worsening of clinical condition
Depression is associated with an increased risk of suicidal thoughts, self-harm, and suicide (suicidal-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks of treatment or longer, patients should be closely monitored until such improvement occurs. Clinical experience has shown that the risk of suicide may increase in the early stages of treatment.
Other psychiatric conditions for which sertraline is prescribed may also be associated with an increased risk of suicidal-related events. In addition, these conditions may coexist with major depressive disorder. Therefore, the same precautions as for patients with major depressive disorder should be taken in patients treated with sertraline for other psychiatric conditions.
Patients with a history of suicidal-related events or those exhibiting a significant degree of suicidal ideation prior to the start of treatment should be closely monitored during treatment. Meta-analyses conducted by the regulatory authorities and others have shown that the risk of suicidal thoughts and/or behavior, as measured by a variety of scales, was higher in children and adolescents treated with antidepressants compared to those treated with placebo.
During treatment, especially in the early stages of treatment and after dose changes, patients should be closely monitored for signs and symptoms of clinical worsening, suicidal behavior, and unusual changes in behavior. Patients (and their caregivers) should be advised to seek medical attention if they experience any signs or symptoms of clinical worsening, suicidal thoughts or behaviors, or unusual changes in behavior.
Children and adolescents
Sertraline should not be used in the treatment of children and adolescents under the age of 18 years, except for patients with obsessive-compulsive disorder aged 6-17 years. In clinical trials, suicidal-related events, including suicidal thoughts and behaviors, and hostility (notably aggression, oppositional behavior, and anger), were more frequently observed in children and adolescents treated with antidepressants compared to those treated with placebo.
If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In a long-term, open-label, naturalistic study of sertraline in 368 patients with a major depressive disorder, which included patients with bipolar disorder, there were no reports of induction of manic or hypomanic episodes.
Abnormal bleeding/bleeding
There have been reports of abnormal bleeding, including gastrointestinal and genitourinary bleeding, during treatment with SSRIs, including sertraline. Caution should be exercised in patients taking SSRIs, especially in combination with other medicinal products known to affect platelet function (e.g., anticoagulants, atypical antipsychotics, and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, and non-steroidal anti-inflammatory drugs [NSAIDs]), as well as in patients with a history of bleeding disorders (see section 4.5).
SSRIs and SNRIs may increase the risk of postpartum hemorrhage (see sections 4.6 and 4.8).
Hyponatremia
Hyponatremia has been reported during treatment with SSRIs and SNRIs, including sertraline. In many cases, hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). There have been reports of serum sodium levels below 110 mmol/L.
In elderly patients, the risk of hyponatremia during treatment with SSRIs or SNRIs, including sertraline, may be greater. This also applies to patients taking diuretics or who are otherwise at risk of dehydration (see section "Use in elderly patients"). In patients with symptomatic hyponatremia, consideration should be given to discontinuing sertraline and instituting appropriate medical treatment. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls.
Symptoms of severe and/or acute hyponatremia include hallucinations, syncope, seizures, coma, and respiratory arrest.
Withdrawal symptoms observed after discontinuation of sertraline
Discontinuation of sertraline (particularly when abrupt) may lead to symptoms such as dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremors, and headache. Generally, these symptoms are mild to moderate, but they can be severe in some cases. They usually occur within the first few days of discontinuing treatment, but there have been reports of such symptoms occurring after a longer period. Generally, these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or longer). It is therefore recommended to gradually reduce the dose of sertraline over a period of at least one to two weeks when discontinuing treatment (see section 4.2).
Akathisia/psychomotor restlessness
Sertraline may be associated with akathisia, characterized by a subjective feeling of restlessness, agitation, and an inability to sit or stand still. This condition is most likely to occur within the first few weeks of treatment. In patients who develop such symptoms, increasing the dose may be harmful.

4.5 Interaction with Other Medicinal Products and Other Forms of Interaction

Concomitant use of sertraline is contraindicated
Monoamine oxidase inhibitors (MAOIs)
Irreversible MAOIs (e.g., selegiline)
Sertraline should not be used in combination with irreversible MAOIs, such as selegiline. Sertraline should not be initiated within at least 14 days after discontinuation of an irreversible MAOI. Sertraline should be discontinued for at least 7 days before starting treatment with an irreversible MAOI (see section 4.3).
Reversible and selective inhibitor of MAO-A (moclobemide)
Due to the risk of serotonin syndrome, sertraline should not be used in combination with a reversible and selective inhibitor of MAO-A, such as moclobemide. After discontinuation of a reversible MAOI, a shorter washout period than 14 days may be used before starting sertraline. Sertraline should be discontinued for at least 7 days before starting treatment with a reversible MAOI (see section 4.3).
Reversible, non-selective inhibitor of MAO (linezolid)
The antibiotic linezolid is a weak, reversible, and non-selective MAOI. It should not be given to patients treated with sertraline (see section 4.3).
Reports of serious adverse events have been received in patients who have recently discontinued an MAOI (e.g., methylene blue) before starting sertraline or who have discontinued sertraline before starting an MAOI. These events have included tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, and hyperthermia with features resembling NMS, seizures, and death.
Pimozide
In a single-dose study of pimozide (2 mg) and sertraline, there was an increase in pimozide levels of approximately 35%. No significant changes in ECG were observed. However, due to the narrow therapeutic index of pimozide and the unknown mechanism of this interaction, concomitant use of sertraline and pimozide is contraindicated (see section 4.3).
Concomitant use of sertraline is not recommended
CNS-active agents, alcohol
Sertraline at a dose of 200 mg per day did not potentiate the cognitive and psychomotor effects of alcohol, carbamazepine, haloperidol, or phenytoin in healthy volunteers. However, it is recommended to avoid alcohol during treatment with sertraline.
Other serotonergic agents
See section 4.4.
Care should be taken when using fentanyl (used in general anesthesia or chronic pain management), other serotonergic agents (including other serotonergic antidepressants, amphetamine derivatives, tryptans), and other opioids (including buprenorphine).
Special warnings
Medicinal products that prolong the QT interval
The risk of QTc prolongation and torsade de pointes-type ventricular tachycardia may be increased during concomitant use of other medicinal products that prolong the QTc interval (e.g., certain antipsychotics and antibiotics) (see sections 4.4 and 5.1).
Lithium
A placebo-controlled study in healthy volunteers has shown that concomitant use of sertraline and lithium does not significantly alter lithium pharmacokinetics, but it does increase tremors (compared to placebo), suggesting a possible pharmacodynamic interaction. When concomitantly using sertraline and lithium, careful monitoring of patients is recommended.
Phenytoin
A placebo-controlled study in healthy volunteers has shown that long-term use of sertraline at a dose of 200 mg per day does not significantly inhibit the metabolism of phenytoin. However, since there have been reports of potentiated effects of phenytoin in patients using sertraline, it is recommended to monitor phenytoin levels at the start of sertraline treatment to adjust the dose as necessary. Additionally, concomitant use of phenytoin may decrease sertraline plasma levels.
Tryptans
Post-marketing reports have described cases of weakness, excessive sweating, and flushing during concomitant use of sertraline and sumatriptan. Symptoms of serotonin syndrome may also occur when using other agents of the same class (tryptans).
Therefore, if concomitant use of sertraline and tryptans is clinically justified, careful observation of the patient is recommended (see section 4.4).
Warfarin
Concomitant use of sertraline at a dose of 200 mg per day and warfarin resulted in a small but statistically significant increase in prothrombin time, which in rare cases may affect INR. Therefore, prothrombin time should be monitored before and after starting and stopping sertraline treatment.
Interactions with other medicinal products, digoxin, atenolol, cimetidine
Concomitant use of cimetidine resulted in a significant decrease in sertraline clearance. The clinical significance of these changes is unknown. Sertraline does not affect the ability of atenolol to exercise its beta-adrenergic blocking effect. No interaction has been observed between sertraline at a dose of 200 mg per day and digoxin.
Medicinal products that affect platelet function
When using medicinal products that affect platelet function (e.g., NSAIDs, acetylsalicylic acid, and ticlopidine) or other medicinal products that may increase the risk of bleeding, concomitantly with SSRIs, including sertraline, the risk of bleeding may be increased (see section 4.4).
Substances that block neuromuscular transmission
SSRIs may decrease the activity of cholinesterase in plasma, which prolongs the neuromuscular blocking effect of mivacurium or other neuromuscular blocking agents.
Medicinal products metabolized by cytochrome P450
Sertraline may act as a mild or moderate inhibitor of cytochrome CYP 2D6. Interaction studies conducted during chronic dosing with sertraline at a dose of 50 mg per day have shown a moderate increase (average 23-37%) in the steady-state concentrations of desipramine (a marker of CYP 2D6 activity) in plasma. Clinically significant interactions may occur with other substrates of CYP 2D6 with a narrow therapeutic index, such as antiarrhythmic agents of class 1C, including propafenone and flecainide, tricyclic antidepressants, and typical antipsychotics, especially at higher sertraline doses.
Sertraline does not inhibit the activity of the isoenzymes CYP 3A4, CYP 2C9, CYP 2C19, and CYP 1A2 to a clinically significant extent. This has been confirmed in in vivointeraction studies with substrates of CYP 3A4 (endogenous cortisol, carbamazepine, terfenadine, alprazolam), a substrate of CYP 2C19 (diazepam), and substrates of CYP 2C9 (tolbutamide, glibenclamide, and phenytoin). In vitrostudies have shown that sertraline does not affect or only slightly inhibits the activity of the CYP 1A2 isoenzyme.
Consuming three glasses of grapefruit juice per day resulted in an increase in sertraline plasma levels of approximately 100% in a study of eight healthy Japanese subjects conducted in a crossover design. Therefore, grapefruit juice should be avoided during treatment with sertraline (see section 4.4).
Based on the interaction study with grapefruit juice, it cannot be excluded that concomitant administration of sertraline with potent CYP3A4 inhibitors, such as protease inhibitors, ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, and nefazodone, may result in even greater exposure to sertraline. This also applies to moderate CYP3A4 inhibitors, such as aprepitant, erythromycin, fluconazole, verapamil, and diltiazem. Potent CYP3A4 inhibitors should be avoided during treatment with sertraline.
Sertraline plasma levels are increased by approximately 50% in poor metabolizers of CYP2C19 compared to extensive metabolizers (see section 5.2). It cannot be excluded that interactions may occur with potent CYP2C19 inhibitors, such as omeprazole, lansoprazole, pantoprazole, rabeprazole, fluoxetine, and fluvoxamine.
Metamizole
Concomitant use of sertraline with metamizole, which is an inducer of enzymes involved in its metabolism, such as CYP2B6 and CYP3A4, may decrease sertraline plasma levels and potentially reduce its clinical efficacy. Therefore, caution should be exercised when co-administering metamizole and sertraline; careful monitoring of clinical response and/or sertraline levels is recommended.

4.6 Fertility, Pregnancy, and Lactation

Pregnancy
There are no adequately controlled studies in pregnant women. However, in animal studies, no teratogenic effects were observed. Animal studies have shown that sertraline has an effect on fertility, probably due to the pharmacodynamic effects of the substance on the mother and/or a direct pharmacodynamic effect on the fetus (see section 5.3).
Epidemiological data suggest that the use of SSRIs and SNRIs in pregnancy, particularly in the third trimester, may increase the risk of postpartum hemorrhage (see sections 4.4 and 4.8).
Neonates should be observed if maternal use of sertraline continues into the later stages of pregnancy, particularly in the third trimester. Following maternal use of sertraline in the later stages of pregnancy, the neonate may experience the following symptoms: respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia, tremors, jitteriness, irritability, lethargy, and constant crying. These symptoms may be due to either serotonergic effects or withdrawal effects.
Epidemiological data indicate an increased risk of persistent pulmonary hypertension of the newborn (PPHN) in association with SSRI treatment in pregnancy, particularly when treatment is taken after the 20th week. The estimated risk of PPHN in the general population is 1-2 per 1000 live births. The use of SSRIs, including sertraline, during pregnancy is not recommended, unless the clinical condition of the woman requires treatment. The potential benefits of treatment should be weighed against the potential risks.
Neonatal withdrawal syndrome has been reported in neonates born to mothers who have used sertraline during pregnancy. If sertraline is used during pregnancy, the neonate should be monitored for signs of withdrawal.
Breast-feeding
Published data indicate that sertraline and its metabolite, N-desmethylsertraline, are present in human milk. In nursing infants, usually very low or undetectable levels of sertraline have been reported. With a single exception of an infant with a serum concentration of sertraline equivalent to about 50% of the mother's concentration, no adverse effects have been reported in breast-fed infants. However, as a precautionary measure, breast-feeding should be avoided in mothers treated with sertraline, unless the benefits of treatment to the mother outweigh the risks to the infant.
Fertility
Animal studies have not shown any effect of sertraline on fertility (see section 5.3). There have been reports of effects of some SSRIs on sperm quality in humans. The clinical significance of these findings is unknown.

• 5.3). There have been reports suggesting that the use of SSRIs in humans may have a reversible effect on sperm quality.

4.7 Effects on Ability to Drive and Use Machines

Clinical pharmacology studies have shown that sertraline does not affect psychomotor function. However, as with other antidepressants, patients should be advised that their ability to drive a car or operate machinery may be impaired.

4.8 Undesirable Effects

The most common undesirable effect is nausea. In the treatment of social anxiety disorder, 14% of male patients treated with sertraline experienced sexual dysfunction (ejaculation failure) compared to 0% in the placebo group. These undesirable effects are dose-dependent and usually transient during continued treatment.
The profile of undesirable effects in double-blind, placebo-controlled studies in patients with OCD, panic disorder, PTSD, and social anxiety disorder was similar to that observed in clinical trials in patients with depression.
Table 1shows the undesirable effects reported in clinical trials and post-marketing experience (frequency not known) in patients treated with sertraline for depression, OCD, panic disorder, PTSD, and social anxiety disorder.

4.9 Overdose

Toxicity
The safety margin of sertraline is dependent on patient population and concomitant medication.
Deaths have been reported in cases of sertraline overdose, alone or in combination with other
medicinal products and/or alcohol. Therefore, any overdose should be treated aggressively.
Symptoms
Symptoms of sertraline overdose include sertraline's adverse reactions such as somnolence, gastrointestinal
disturbances (including nausea and vomiting), tachycardia, tremor, agitation, and dizziness. Rarely,
reported symptoms include coma.
Following sertraline overdose, cases of QTc prolongation or torsades de pointes have been reported,
and therefore ECG monitoring is recommended (see sections 4.4, 4.5, and 5.1).
Management
There is no specific antidote for sertraline. Establish and maintain an airway, ensure adequate oxygenation
and ventilation if necessary. Activated charcoal, which may be used with a laxative, may be as effective
as or more effective than ipecac in some patients, and should be considered. Induction of emesis is not
recommended. Cardiac and vital signs should be monitored, and general supportive measures should be
used as needed. Due to the large volume of distribution of sertraline, forced diuresis, dialysis, haemoperfusion,
and exchange transfusion are unlikely to be of benefit.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic Properties

Pharmacotherapeutic Group: Selective serotonin reuptake inhibitors (SSRIs), ATC Code: N06AB06
Mechanism of Action
Sertraline is a potent and selective inhibitor of neuronal serotonin reuptake in vitro, which results in
the potentiation of serotonin activity in the central nervous system. It has only very weak inhibitory
effects on norepinephrine and dopamine reuptake. At clinically relevant doses, sertraline blocks
serotonin uptake in human platelets. In animal studies, sertraline did not exhibit stimulant, sedative, or
anticholinergic activity or cardiovascular effects. In vitro studies indicate that sertraline has no significant
affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic,
serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors. Chronic administration of
sertraline in animals was associated with downregulation of brain norepinephrine receptors, as has been
observed with other clinically effective antidepressant and antiobsessional agents.
Clinical Efficacy and Safety
Major Depressive Episodes
A study was conducted in outpatients meeting Diagnostic and Statistical Manual of Mental Disorders
III (DSM-III) criteria for major depressive disorder who had responded to sertraline during an initial 8-
week open trial. Responders (n=295) were randomized to continuation for 44 weeks on double-
blind sertraline (dose 50-200 mg/day) or placebo. The proportion of patients who did not experience a
depressive episode was significantly higher for patients taking sertraline than for those on placebo. The
mean sertraline dose for completers was 70 mg/day. The rate of response was 83.4% for sertraline and
60.8% for placebo.
Post-Traumatic Stress Disorder (PTSD)
Data from three studies in PTSD, mainly in outpatients, showed a lower response to sertraline in men than
in women. In two studies in the general population with positive results, the response to sertraline in men
and women was similar (men: 53.9% vs. 38.2%, women: 57.2% vs. 34.5%). The number of male and
female patients in the combined general population studies was 184 and 430, respectively, making the
results in women more robust; in men, other baseline factors such as greater frequency of substance
abuse, longer duration, source of trauma, etc., may have influenced the outcome, reducing the effect of
the treatment.
Electrocardiogram (ECG) Changes
A dedicated QTc interval study was conducted in 54 healthy subjects, comparing the QTc interval after
administration of sertraline (50 mg, 100 mg, 200 mg, and 400 mg once daily for 10 days) with that
after administration of placebo. The upper bound of the 90% confidence interval for the largest
mean difference from placebo at the 400 mg dose was 11.7 ms, which is less than the predefined
threshold of 20 ms. The dose-dependent nature of the effect of sertraline on the QTc interval was
examined in this study. The estimated difference in QTc interval (sertraline - placebo) was 11.7 ms at
the 400 mg dose, with an upper 90% confidence interval bound of 15.4 ms. In this study, there were
no reports of any adverse reactions, including cardiac adverse reactions or cardiac arrhythmias, in any
subject at doses up to 400 mg/day.
Paediatric Population with Obsessive-Compulsive Disorder (OCD)
The safety and efficacy of sertraline were evaluated in a 12-week, multicentre, randomized, double-
blind, placebo-controlled study in 281 paediatric outpatients, ages 6 to 17, with a DSM-IV diagnosis
of OCD. Patients were randomized to either sertraline (n=142) or placebo (n=139) for 12 weeks. The
initial dose was 25 mg in children <12 years of age and 50 mg in adolescents. doses were titrated over
the first four weeks to a maximum dose of 200 mg/day. At baseline, 28% of patients had co-existing
anxiety disorders; 22% had co-existing depressive disorders; 20% had co-existing attention deficit
hyperactivity disorder (ADHD); and 21% had co-existing tic disorders. Patients receiving sertraline
experienced a mean reduction of 32.7% on the Children's Yale-Brown Obsessive Compulsive Scale
(CY-BOCS) total score, which was significantly greater than the 20.9% mean reduction in placebo-
treated patients (p=0.005). Analyses for age and gender effects on outcomes did not suggest any
significant differences in treatment outcome. In a long-term, open-label study in paediatric patients with
OCD, 192 patients were treated with sertraline (dose range: 25-200 mg) for a minimum of 24 weeks and
for a maximum of 52 weeks. No patient reported a serious adverse event during the study. The most
common adverse events reported were similar to those observed in the 12-week, double-blind, placebo-
controlled study.
SPRITES Study
A 3-year, observational, non-randomized study was conducted to evaluate the long-term safety of
sertraline in 941 paediatric patients (6-16 years) with a diagnosis of OCD, depression, or other anxiety
disorders. Patients were treated with sertraline, with or without concomitant psychotherapy, for a
minimum of 6 months and a maximum of 36 months. The study included 473 patients with a primary
diagnosis of OCD, 172 patients with a primary diagnosis of depression, and 296 patients with other
anxiety disorders. The most common adverse reactions were headache (24.6%), insomnia (23.1%),
diarrhoea (20.5%), and nausea (19.2%). The majority of adverse reactions were mild to moderate in
severity and consistent with the known safety profile of sertraline. The study did not reveal any long-
term safety concerns in the paediatric population.

5.2 Pharmacokinetic Properties

Absorption
After oral administration of sertraline, the peak plasma levels of sertraline occur after approximately
4.5 to 8.4 hours. Food does not affect the bioavailability of sertraline.
Distribution
About 98% of the circulating sertraline is bound to plasma proteins.
Metabolism
Sertraline undergoes extensive first-pass metabolism. Based on clinical and in vitrodata, it is
estimated that sertraline is metabolized by multiple pathways, including CYP3A4, CYP2C19 (see section
4.5), and CYP2B6. Sertraline and its major metabolite, N-desmethylsertraline, are also substrates of
P-glycoprotein in vitro.
Elimination
The mean elimination half-life of sertraline is approximately 26 hours (range 22-36 hours). Based on
pharmacokinetic studies, after a single dose of sertraline, the peak plasma concentration of sertraline
occurs at approximately 4.5 to 8.4 hours. The elimination half-life of N-desmethylsertraline ranges from
62 to 104 hours. Both sertraline and N-desmethylsertraline are extensively metabolized in humans, and
their metabolites are excreted in feces and urine in equal amounts. Only a small amount (<0.2%) of
unchanged sertraline is excreted in the urine.
Linearity/Non-Linearity
The pharmacokinetic profile of sertraline is dose-proportional in the range of 50 to 200 mg.
Pharmacokinetics in Special Populations
Paediatric Population with OCD
The pharmacokinetics of sertraline were studied in 29 children, aged 6 to 12 years, and 32 adolescents,
aged 13 to 17 years, who received sertraline, 50-200 mg/day, for 21-28 days. The sertraline plasma
levels were similar to those observed in adults. The mean plasma half-life of sertraline was 21.4 hours in
children (6-12 years) and 22.4 hours in adolescents (13-17 years).
Geriatric and Non-Geriatric Patients
The pharmacokinetic profile of sertraline is not significantly different in geriatric and non-geriatric
patients.
Patients with Hepatic Impairment
The elimination half-life of sertraline is longer and the AUC is increased in patients with liver disease.
Patients with Renal Impairment
No significant accumulation of sertraline was observed in patients with mild to severe renal impairment.
Pharmacogenomics
The plasma levels of sertraline were approximately 50% higher in poor metabolizers of CYP2C19
compared to extensive metabolizers. The clinical significance of this finding is unknown; the dose of
sertraline should be adjusted based on clinical response.

5.3 Preclinical Safety Data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential. In animal studies, no
effects on fertility were observed. Fetal toxicity (e.g., delayed ossification) has been observed in rats and
rabbits when sertraline was administered during pregnancy. When pregnant rats were given sertraline
during the period of organogenesis, there was an increased incidence of fetal losses and neonatal deaths.
Studies in Juvenile Animals
In a juvenile toxicity study, where sertraline was administered orally to juvenile rats from postnatal day
21 to 56, the following effects were observed: a delay in sexual maturation in both males and females
(≥10 mg/kg), decreased growth, and increased motor activity (at doses ≥ 80 mg/kg). There were no
effects of sertraline on learning and memory or on the reproductive indices in the F1 generation.
However, the number of stillbirths was increased and the pup survival rate was decreased at the highest
dose (200 mg/kg). The no-effect dose for these findings was not determined. The clinical significance of
these effects is unknown.

6. PHARMACEUTICAL PARTICULARS

6.1 List of Excipients

Calcium phosphate dibasic dihydrate
Microcrystalline cellulose
Sodium carboxymethyl cellulose (Type A)
Hydroxypropyl cellulose
Talc
Magnesium stearate
Coating:
Hypromellose
Titanium dioxide (E 171)
Talc
Propylene glycol

6.2 Incompatibilities

None known.

6.3 Shelf Life

5 years

6.4 Special Precautions for Storage

No special requirements.

6.5 Nature and Contents of Container

PVC/Aluminium blister pack, in a cardboard box.
Pack sizes: 28 or 84 film-coated tablets

6.6 Special Precautions for Disposal and Other Handling

For use
No special requirements.

7. MARKETING AUTHORISATION HOLDER

AND MANUFACTURER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

8. MARKETING AUTHORISATION NUMBERS

Asentra, 50 mg: Marketing Authorisation Number 9632
Asentra, 100 mg: Marketing Authorisation Number 9633

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

DATE OF REVISION OF THE TEXT

Date of first authorisation: 05.12.2002
Date of last renewal: 22.11.2013

10. DATE OF REVISION OF THE TEXT

• Country of registration
  Poland
• Active substance
  sertraline
• Prescription required
  Yes
• Manufacturer
  Krka, d.d., Novo mesto
• Importer
  Krka, d.d., Novo mesto
• This information is for reference only and does not constitute medical advice. Always consult a licensed doctor before taking any medication. Oladoctor is not responsible for medical decisions based on this content.

Talk to a doctor online

Need help understanding this medicine or your symptoms? Online doctors can answer your questions and offer guidance.

5.0(21)

Ekaterina Agapova

Neurology8 years of experience

Dr. Ekaterina Agapova is a neurologist specialising in the diagnosis and treatment of neurological conditions and chronic pain. She provides online consultations for adults, combining evidence-based medicine with a personalised approach.

She offers expert care for:

• Headaches and migraines, including tension-type and cluster headaches.
• Neck and back pain, both acute and chronic.
• Chronic pain syndromes – fibromyalgia, neuropathic pain, post-traumatic pain.
• Mononeuropathies – carpal tunnel syndrome, trigeminal neuralgia, facial nerve palsy.
• Polyneuropathies – diabetic, toxic, and other types.
• Multiple sclerosis – diagnosis, monitoring, long-term support.
• Dizziness and coordination disorders.
• Sleep disturbances – insomnia, daytime sleepiness, fragmented sleep.
• Anxiety, depression, and stress-related conditions.

Dr. Agapova helps patients manage complex neurological symptoms like pain, numbness, weakness, poor sleep, and emotional distress. Her consultations focus on accurate diagnosis, clear explanation of findings, and tailored treatment plans.

If you’re struggling with chronic pain, migraines, nerve disorders, or sleep problems, Dr. Agapova offers professional guidance to restore your well-being.

Book a video appointment

More times

5.0(37)

Yevgen Yakovenko

General surgery11 years of experience

Dr. Yevgen Yakovenko is a licensed surgeon and general practitioner in Spain and Germany. He specialises in general, paediatric, and oncological surgery, internal medicine, and pain management. He offers online consultations for adults and children, combining surgical precision with therapeutic support. Dr Yakovenko works with patients across different countries and provides care in Ukrainian, Russian, English, and Spanish.

Areas of medical expertise:

• Acute and chronic pain: headaches, muscle and joint pain, back pain, abdominal pain, postoperative pain. Identifying the cause, selecting treatment, and creating a care plan.
• Internal medicine: heart, lungs, gastrointestinal tract, urinary system. Management of chronic conditions, symptom control, second opinions.
• Pre- and postoperative care: risk assessment, decision-making support, follow-up after surgery, rehabilitation strategies.
• General and paediatric surgery: hernias, appendicitis, congenital conditions, both planned and urgent surgeries.
• Injuries and trauma: bruises, fractures, sprains, soft tissue damage, wound care, dressing, referral when in-person care is required.
• Oncological surgery: diagnosis review, treatment planning, and long-term follow-up.
• Obesity treatment and weight management: a medical approach to weight loss, including assessment of underlying causes, evaluation of comorbidities, development of a personalised plan (nutrition, physical activity, pharmacotherapy if needed), and ongoing progress monitoring.
• Imaging interpretation: analysis of ultrasound, CT, MRI, and X-ray results, surgical planning based on imaging data.
• Second opinions and medical navigation: clarifying diagnoses, reviewing current treatment plans, helping patients choose the best course of action.

Experience and qualifications:

• 12+ years of clinical experience in university hospitals in Germany and Spain.
• International education: Ukraine – Germany – Spain.
• Member of the German Society of Surgeons (BDC).
• Certified in radiological diagnostics and robotic surgery.
• Active participant in international medical conferences and research.

Dr Yakovenko explains complex topics in a clear, accessible way. He works collaboratively with patients to analyse health issues and make evidence-based decisions. His approach is grounded in clinical excellence, scientific accuracy, and respect for each individual.

If you are unsure about a diagnosis, preparing for surgery, or want to discuss your test results – Dr Yakovenko will help you evaluate your options and move forward with confidence.

Book a video appointment

More times

5.0(12)

Jonathan Marshall Ben Ami

Family medicine8 years of experience

Dr. Jonathan Marshall Ben Ami is a licensed family medicine doctor in Spain. He provides comprehensive care for adults and children, combining general medicine with emergency care expertise to address both acute and chronic health concerns.

Dr. Ben Ami offers expert diagnosis, treatment, and follow-up for:

• Respiratory infections (cold, flu, bronchitis, pneumonia).
• ENT conditions such as sinusitis, ear infections, and tonsillitis.
• Digestive issues including gastritis, acid reflux, and irritable bowel syndrome (IBS).
• Urinary tract infections and other common infections.
• Management of chronic diseases: high blood pressure, diabetes, thyroid disorders.
• Acute conditions requiring urgent medical attention.
• Headaches, migraines, and minor injuries.
• Wound care, health check-ups, and ongoing prescriptions.

With a patient-focused and evidence-based approach, Dr. Ben Ami supports individuals at all stages of life — offering clear medical guidance, timely interventions, and continuity of care.

Book a video appointment

More times

5.0(4)

Salome Akhvlediani

Pediatrics11 years of experience

Dr Salome Akhvlediani is a paediatrician providing online consultations for children of all ages. She supports families with preventive care, diagnosis, and long-term management of both acute and chronic conditions.

Her areas of focus include:

• Fever, infections, cough, sore throat, and digestive issues.
• Preventive care – vaccinations, regular check-ups, and health monitoring.
• Allergies, asthma, and skin conditions.
• Nutritional advice and healthy development support.
• Sleep difficulties, fatigue, and behavioural concerns.
• Ongoing care for chronic or complex health conditions.
• Guidance for parents and follow-up after medical treatment.

Dr Akhvlediani combines professional care with a warm, attentive approach – helping children stay healthy and supporting parents at every stage of their child’s growth.

Book a video appointment

More times

View all doctors

Get updates and exclusive offers

Be the first to know about new services, marketplace updates, and subscriber-only promos.

Subscribe

Follow us on social media